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GeneBe

2-111123784-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_138621.5(BCL2L11):c.39C>T(p.Asp13=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00411 in 1,448,578 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0034 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0042 ( 19 hom. )

Consequence

BCL2L11
NM_138621.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.51
Variant links:
Genes affected
BCL2L11 (HGNC:994): (BCL2 like 11) The protein encoded by this gene belongs to the BCL-2 protein family. BCL-2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. The protein encoded by this gene contains a Bcl-2 homology domain 3 (BH3). It has been shown to interact with other members of the BCL-2 protein family and to act as an apoptotic activator. The expression of this gene can be induced by nerve growth factor (NGF), as well as by the forkhead transcription factor FKHR-L1, which suggests a role of this gene in neuronal and lymphocyte apoptosis. Transgenic studies of the mouse counterpart suggested that this gene functions as an essential initiator of apoptosis in thymocyte-negative selection. Several alternatively spliced transcript variants of this gene have been identified. [provided by RefSeq, Jun 2013]
MIR4435-2HG (HGNC:35163): (MIR4435-2 host gene)

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-111123784-C-T is Benign according to our data. Variant chr2-111123784-C-T is described in ClinVar as [Benign]. Clinvar id is 775750.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.51 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 520 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BCL2L11NM_138621.5 linkuse as main transcriptc.39C>T p.Asp13= synonymous_variant 2/4 ENST00000393256.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BCL2L11ENST00000393256.8 linkuse as main transcriptc.39C>T p.Asp13= synonymous_variant 2/41 NM_138621.5 P1O43521-1
MIR4435-2HGENST00000645030.2 linkuse as main transcriptn.453-86862G>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00342
AC:
520
AN:
152118
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000918
Gnomad AMI
AF:
0.0231
Gnomad AMR
AF:
0.00301
Gnomad ASJ
AF:
0.0156
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00124
Gnomad FIN
AF:
0.00113
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00489
Gnomad OTH
AF:
0.00478
GnomAD3 exomes
AF:
0.00345
AC:
534
AN:
154634
Hom.:
1
AF XY:
0.00366
AC XY:
299
AN XY:
81794
show subpopulations
Gnomad AFR exome
AF:
0.000741
Gnomad AMR exome
AF:
0.00287
Gnomad ASJ exome
AF:
0.0166
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00112
Gnomad FIN exome
AF:
0.00143
Gnomad NFE exome
AF:
0.00482
Gnomad OTH exome
AF:
0.00373
GnomAD4 exome
AF:
0.00419
AC:
5431
AN:
1296342
Hom.:
19
Cov.:
32
AF XY:
0.00399
AC XY:
2517
AN XY:
630982
show subpopulations
Gnomad4 AFR exome
AF:
0.000813
Gnomad4 AMR exome
AF:
0.00353
Gnomad4 ASJ exome
AF:
0.0128
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00150
Gnomad4 FIN exome
AF:
0.00173
Gnomad4 NFE exome
AF:
0.00457
Gnomad4 OTH exome
AF:
0.00412
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00342
AC:
520
AN:
152236
Hom.:
0
Cov.:
33
AF XY:
0.00316
AC XY:
235
AN XY:
74434
show subpopulations
Gnomad4 AFR
AF:
0.000915
Gnomad4 AMR
AF:
0.00301
Gnomad4 ASJ
AF:
0.0156
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00124
Gnomad4 FIN
AF:
0.00113
Gnomad4 NFE
AF:
0.00490
Gnomad4 OTH
AF:
0.00473
Alfa
AF:
0.00248
Hom.:
0
Bravo
AF:
0.00361
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.53
Cadd
Benign
11
Dann
Benign
0.63
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs112446582; hg19: chr2-111881361; COSMIC: COSV100427578; API